Aging in humans is associated with a striking deficiency in adrenal production of androgens. Reduced levels of adrenal androgens have been correlated with increased indicence of many sequelae of aging such as cardiovascular disease, cancer, insulin resistance, hyperlipidemia, and impaired immune competence. The mechanisms for age-associated reductions in adrenal androgen production are unknown. It also is not clear if aging effects adrenal function in men and women in similar manners or whether there are race related differences in adrenal function in young or elderly humans. We propose to continue our studies on the effect of aging on the adrenal steroid biosynthetic pathway, particularly in aging African Americans, in whoem little is established regarding adrenal corticosteroid or androgen production. These studies will be condectted by means of dynamic functional testing of adrenal responses to graded doses of ACTH in aged men and women compared to young adults. The results of these studies are expected to provide both a characterization of adrenal function in aged adults and also to suggest the mechanisms whereby such function is altered in normal aging adults. The impact of hormone replacement therapy in postmenopausal women on adrenal steroidogenic responses also will be determined.